UBL4A
protein-codingubiquitin like 4A, the group of GET4-GET5 transmembrane domain recognition complex subunits|BAG6 complex
Gene summary
Enables protein-folding chaperone binding activity. Involved in several processes, including post-translational protein targeting to endoplasmic reticulum membrane; regulation of protein stability; and tail-anchored membrane protein insertion into ER membrane. Located in cytosol; membrane; and nucleoplasm. Part of BAT3 complex. [provided by Alliance of Genome Resources, Jun 2026]
- UBL4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to UBL4A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014235.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 1 | 1 | 6 | ||
| missense | 21 | 1 | 22 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 31 | 2 | 1 | 34 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055050.1 | 4 | MANE Select | |
| Ensembl | ENSP00000358674.4 | 4 | MANE Select | |
| Ensembl | ENSP00000358667.4 | 5 | Standard | |
| Ensembl | ENSP00000358667.4 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cellular protein modification process
- tail-anchored membrane protein insertion into ER membrane
Molecular Function
- protein binding
- ubiquitin-like protein transferase activity
- chaperone binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369660
- Coding exons
- 4
- Length
- 2954
- Individuals with no LoFs
- 123148
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 123149
- p
- 0.00000406
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.704 | 40 | 54.6 | 0.732 | 0.00000431 | 991 |
| Missense (PolyPhen) | 9 | 18.797 | 0.47881 | 392 | ||
| Synonymous | -1.07 | 34 | 27.0 | 1.26 | 0.00000218 | 336 |
| Loss of Function | 1.38 | 1 | 3.96 | 0.252 | 2.58e-7 | 77 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000013 | 0.0000091 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: As part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, maintains misfolded and hydrophobic patches-containing proteins in a soluble state and participates to their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation (PubMed:20676083, PubMed:21636303, PubMed:21743475, PubMed:28104892). The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Recruited to ribosomes, it interacts with the transmembrane region of newly synthesized tail-anchored proteins and together with SGTA and ASNA1 mediates their delivery to the endoplasmic reticulum (PubMed:20676083, PubMed:28104892, PubMed:25535373). Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated and sorted to the proteasome (PubMed:28104892). Similarly, the BAG6/BAT3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum (PubMed:21743475). The BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome (PubMed:21636303). {ECO:0000269|PubMed:20676083, ECO:0000269|PubMed:21636303, ECO:0000269|PubMed:21743475, ECO:0000269|PubMed:25535373, ECO:0000269|PubMed:28104892}.;
Recessive Scores
- pRec
- 0.269
Intolerance Scores
- LoFtool
- 0.313
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 49.39
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.539
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |